Rapid Characterization of Drug-drug Interaction in Plasma Protein Binding using a Surface Plasmon Resonance Biosensor

Abstract

High-throughput characterization of drug-drug interactions in plasma protein binding was demonstrated by using a surface plasmon resonance (SPR) biosensor. The method used in this study enabled the discrimination between the two modes of binding inhibition, direct competition and negative allosteric effect, which was difficult in conventional SPR approaches. Two theoretical equations were used representing SPR binding response for directly competitive binding or for independent binding. The experimental binding data for human serum albumin was processed by non-linear least squared regression of the equations. By this approach, drug-drug interactions were classified into three modes, direct competition, independent binding, and allosteric interaction, which were almost consistent with previous reports. In addition, dissociation constants were also estimated roughly for direct competition and for independent binding. The analytical throughput was almost as high as in the previous reports; three minutes per injection. This method is a powerful tool for the characterization of drug-drug interaction at an early stage of new drug development.